The etiology of Acquired Immune Deficiency Syndrome (AIDS) is not known, although currently a variety of microbial agents has been proposed as playing a causative role. Since opportunistic infections with a variety of such viral, bacterial, fungal and parasitic agents occurs characteristically in AIDS, the question of whether an agent is etiologic or opportunistic arises frequently. The recovery of an infectious agent(s) or the demonstration of an antibody response to such an agent prior to the diagnosis of AIDS would provide evidence for primary infection with a putative etiological agent. The major obstacle to efforts directed at cultivation or serological characterization of putative etiological agents has been the availability of early specimens obtained prior to the onset of AIDS. These specimens would be most likely to contain the agent, and even earlier sera would be required to represent pre-exposure sera. In response to these needs, an intramural research contract was developed with the New York Blood Center and Memorial Sloan Kettering Cancer Center to collect specimens in a prospective fashion from 325 homosexual males. Three populations are being recruited: patients with lymphadenopathy (100), normal plasma donors (175) and normal homosexual males from a geographically distinct area in New York State (50). Specimens of peripheral blood leukocytes, plasma, serum, semen, urine, saliva and stool will be collected at 1 to 4 month intervals, along with epidemiological information. Specimens will be stored in an NIAID Repository until cases of AIDS are identified in the study population. At that time, appropriate specimens will be studied intensively for the presence of agents, and paired sera will be examined for the development of antibody to various candidate agents.